Significant advances in cancer chemotherapy have occurred over the last decade, but target-specific and effective drug delivery mechanisms remain an unmet need in the treatment of cancer. This application represents a unique combination of expertise in chemistry and medicine that will enable the development and testing of novel drug delivery approaches. The chemistry utilizes carbon dioxide as a solvent in the preparation of nanoparticles whose size, shape, and surroundings can be well-controlled for use in the development of new Pharmaceuticals and molecular sensors for imaging. The nanoparticles will be comprised of small molecules (drugs) and, when needed, a polymer coating for controlled delivery and release. These nanosized drugs will allow for targeted delivery to, e.g., a cancer cell, allowing for lower doses of drugs to be used and therefore will also reduced unwanted side-effects and damage to healthy cells. The Specific Aims are: 1. Develop a supercritical antisolvent process to form encapsulated nanoparticles of controlled size and morphology. 2. Encapsulate selected nanoparticles in situ in the supercritical antisolvent. 3. Evaluate selected nanoparticles in animal models Lav Summary: Supercritical antisolvent synthesis provides a way to create nanoparticles with a wide variety of contents, sizes and coatings. By forming nanoparticles containing drugs with custom coatings, it will be possible to target drugs to specific destinations in the body. One benefit may be a new form of chemotherapy with much lower dosages of drugs and lower side effects in the patient. [unreadable] [unreadable] [unreadable]